This project proposes to develop a new radiotracer for producing external images of sites of thrombosis. Preliminary data have shown that radioiodinated Fragment E1 is a specific marker for both fresh and aged thrombi in vivo, and has a more rapid blood clearance rate than fibrinogen. Initial clinical trials of the I-123-labeled Fragment E1 in patients with thrombosis resulted in positive images when thrombi were proven to exist, but the images did not provide adequate delineation of the thrombi. The aims of this project are threefold. The first step is to overcome the difficulties of the radioiodine label by labeling instead with In-111 or Tc-99m attached to the molecule via a bifunctional chelating moiety; this should improve the specific activity of the labeled Fragment E1 for improved image quality, and it should increase the ease of labeling. The second step will be to test the new labeled Fragment E1 in animal models of thrombosis to determine its ability to produce external images of thrombi using a scintillation camera. The last phase of the project will be to carry out initial clinical trials of the new labeled Fragment E1 in patients with documented thrombosis, correlating the Fragment E1 images with the results of contrast venography. It is hoped that the new radiotracer will provide a much-needed sensitive, specific, and rapid test for existing thromboembolic disease.